The main purpose of this proposal is to determine the occurrence of metabolic changes, induced by acute or chronic alcohol intoxications, in discrete loci of the central nervous system. Initial studies will employ the quantitative histochemical techniques to determine alterations in the contents of certain amino acids considered to be putative neurotransmitters. Enzymes associated with these amino acids will also be studied in normal and ethanol-treated animals. The investigation will be extended in the future to address the concomitant changes in carbohydrate metabolism and in intermediates of the citric acid cycle. These approaches can provide information concerning the localizations of the pharmacological effects of alcohol in specific neuronal groupings of the brain and spinal cord. By using inbred strains of mice which possess different preference and brain sensitivity to alcohol, it is hoped to gain insight into the biochemical factors shaping alcohol preference. A second goal is to compare the metabolic changes associated with chronic alcoholism, vitamin B6 deficiency, vitamin B6 deficiency plus chronic alcoholism, and the alcohol withdrawal syndrome. Finally, the biochemical mechanisms underlying the interaction of alcohol with drugs such as the barbiturates will be investigated.